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The dysregulation of the rat sarcoma (RAS) signaling pathway, particularly the MAPK/ERK cascade, is a hallmark of many cancers, leading to uncontrolled cellular proliferation and resistance to apoptosis-inducing treatments. Dysregulation of the MAPK/ERK pathway is common in various cancers including pancreatic, lung, and colon cancers, making it a critical target for therapeutic intervention. Natural compounds, especially phytochemicals, offer a promising avenue for developing new anticancer therapies due to their potential to interfere with these signaling pathways. This study investigates the potential of anticancer phytochemicals to inhibit the MAPK/ERK pathway through molecular docking and simulation techniques. A total of 26 phytochemicals were screened from an initial set of 340 phytochemicals which were retrieved from Dr. Duke’s database using in silico methods for their binding affinity and stability. Molecular docking was performed to identify key interactions with ERK2, followed by molecular dynamics (MD) simulations to evaluate the stability of these interactions. The study identified several phytochemicals, including luteolin, hispidulin, and isorhamnetin with a binding score of -10.1±0 Kcal/mol, -9.86±0.15 Kcal/mol, -9.76±0.025 Kcal/mol, respectively as promising inhibitors of the ERK2 protein. These compounds demonstrated significant binding affinities and stable interactions with ERK2 in MD simulation studies up to 200ns, particularly at the active site. The radius of gyration analysis confirmed the stability of these phytochemical-protein complexes’ compactness, indicating their potential to inhibit ERK activity. The stability and binding affinity of these compounds suggest that they can effectively inhibit ERK2 activity, potentially leading to more effective and less toxic cancer treatments. The findings underscore the therapeutic promise of these phytochemicals, which could serve as a basis for developing new cancer therapies.

Inhibition of acetylcholinesterase (AChE) is a crucial target in the treatment of Alzheimer’s disease (AD). Common anti-acetylcholinesterase drugs such as Galantamine, Rivastigmine, Donepezil, and Tacrine have significant inhibition potential. Due to side effects and safety concerns, we aimed to investigate a wide range of phytochemicals and structural analogues of these compounds. Compounds similar to the established drugs, and phytochemicals were investigated as potential inhibitors for AChE in treating AD. A total of 2,270 compound libraries were generated for further analysis. Initial virtual screening was performed using Pyrx software, resulting in 638 molecules showing higher binding affinities compared to positive controls Tacrine (-9.0 kcal/mol), Donepezil (-7.3 kcal/mol), Galantamine (-8.3 kcal/mol), and Rivastigmine (-6.4 kcal/mol). Subsequently, ADME properties were assessed, including blood-brain barrier permeability and Lipinski’s rule of five violations, leading to 88 compounds passing the ADME analysis. Among the rivastigmine analogous, [3-(1-methylpiperidin-2-yl)phenyl] N,N-diethylcarbamate showed interaction with Tyr123, Tyr336, Tyr340, Phe337, Trp285 residues of AChE. Tacrine similar compounds, such as 4-amino-2-styrylquinoline, exhibited bindings with Tyr123, Phe337, Tyr336, Trp285, Trp85, Gly119, and Gly120 residues. A phytocompound (bisdemethoxycurcumin) showed interaction with Trp285, Tyr340, Trp85, Tyr71, and His446 residues of AChE with favourable binding. These findings underscore the potential of these compounds as novel inhibitors of AChE, offering insights into alternative therapeutic avenues for AD. A 100ns simulation analysis confirmed the stability of protein-ligand complex based on the RMSD, RMSF, ligand properties, PCA, DCCM and MMGBS parameters. The investigation suggested 3 ligands as a potent inhibitor of AChE which are [3-(1-methylpiperidin-2-yl)phenyl] N,N-diethylcarbamate, 4-Amino-2-styrylquinoline and bisdemethoxycurcumin. Furthermore, investigation, including in-vitro and in-vivo studies, is needed to validate the efficacy, safety profiles, and therapeutic potential of these compounds for AD treatment.

Dengue fever, caused by the dengue virus (DENV), presents a significant global health concern, with millions of cases reported annually. Despite significant progress in understanding Dengue fever, effective prognosis and treatment remain elusive due to the complex clinical presentations and limitations in current diagnostic methods. The virus, transmitted primarily by the Aedes aegypti mosquito, exists in four closely related forms, each capable of causing flu-like symptoms ranging from mild febrile illness to severe manifestations such as plasma leakage and hemorrhagic fever. Although advancements in diagnostic techniques have been made, early detection of severe dengue remains difficult due to the complexity of its clinical presentations. This study conducted a comprehensive analysis of differential gene expression in dengue fever patients using multiple microarray datasets from the NCBI GEO database. Through bioinformatics approaches, 163 potential biomarker genes were identified, with some overlapping previously reported biomarkers and others representing novel candidates. Notably, AURKA, BUB1, BUB1B, BUB3, CCNA2, CCNB2, CDC6, CDK1, CENPE, EXO1, NEK2, ZWINT, and STAT1 were among the most significant biomarkers. These genes are involved in critical cellular processes, such as cell cycle regulation and mitotic checkpoint control, which are essential for immune cell function and response. Functional enrichment analysis revealed that the dysregulated genes were predominantly associated with immune response to the virus, cell division, and RNA processing. Key regulatory genes such as AURKA, BUB1, BUB3, and CDK1 are found to be involved in cell cycle regulation and have roles in immune-related pathways, underscoring their importance in the host immune response to Dengue virus infection. This study provides novel insights into the molecular mechanisms underlying Dengue fever pathogenesis, highlighting key regulatory genes such as AURKA and CDK1 that could serve as potential biomarkers for early diagnosis and targets for therapeutic intervention, paving the way for improved management of the disease.

Glycogen synthase kinase-3 beta (GSK-3β) is a serine/threonine kinase implicated in various diseases such as Alzheimer’s, diabetes, and cancer, making it a pivotal therapeutic target. This study uniquely integrates a curated phytochemical library with comprehensive ADMET filtering and 200 ns molecular dynamics (MD) simulations to identify stable GSK-3β inhibitors, offering deeper mechanistic and dynamic insights than previous docking-based studies. ADMET profiling shortlisted 49 compounds, with uzarigenin, jatrophone, chrysin, and podolide exhibiting superior binding affinities compared to Tideglusib (-8.53 kcal/mol). Among these, jatrophone displayed the highest binding affinity (9.00 kcal/mol), followed by uzarigenin (8.63 kcal/mol) and podolide (8.60 kcal/mol), indicating stronger interactions with GSK-3β. Molecular dynamics simulations confirmed stability for uzarigenin and podolide over 200 nanoseconds, supported by RMSD, SASA, and Rg analyses. Principal component and covariance analyses revealed strong residue interactions in these complexes. KEGG pathway analysis highlighted the role of GSK-3β inhibitors in Alzheimer’s disease, Wnt signaling, and cancer pathways. This study identifies phytochemicals with potential therapeutic applications for neurodegenerative, cancer, and metabolic diseases, warranting further experimental validation.

Background Camellia sinensis, widely consumed as tea, is the second most popular beverage globally and is valued for its health benefits. However, environmental stressors pose a significant challenge to the tea industry. This study investigates the potential of shikimic acid (ShA) and its derivative, salicylic acid (SA), as inducers to enhance polyphenol content and antioxidant activity across different growth stages. Results Experiments on Biclonal Tea Stock 1 (BTS1) family plants, including 4‐month‐old seedlings and 2‐year‐old plants, revealed significant increases in polyphenol levels and antioxidant activity following induction, though effects diminished over time. SA provided a stronger initial boost, whereas ShA sustained longer‐lasting effects. Two‐year‐old plants exhibited greater baseline polyphenol levels and a stronger response to induction than seedlings. A strong correlation between polyphenol accumulation and antioxidant activity was also observed. Molecular docking simulations suggested that SA signaling facilitates NPR1‐TGA and NPR1‐WRKY binding to the PAL promoter, enhancing PAL gene transcription. Additionally, polyphenols such as flavones, p‐coumaric acid, gallic acid, and caffeic acid were found to interact with the PAL enzyme through mechanisms similar to that of trans‐cinnamic acid and may, therefore, act as feedback inhibitors in a manner analogous to trans‐cinnamic acid. Conclusion These findings provide novel insights into optimizing tea plant defenses and enhancing polyphenol‐related health benefits, offering potential strategies for improving tea quality and resilience against environmental stress.